Antineoplastic treatment regimens consisting of chemotherapy and/or irradiation often result in a dysfunction of hematopoietic precursor cells of the granulocyte-macrophage lineage, with an increased morbidity and mortality in cancer patients. We were therefore interested in testing the ability of selected Biological Response Modifiers (BRMs) to modulate growth and differentiation of granulocyte-macrophage precursor cells (GM-CFU-C) by stimulating the release of specific granulocyte-macrophage colony-stimulating factors (GM-CSF). Release of GM-CSF by murine and human monocytes/macrophages and bone marrow cells in vitro could be induced by Poly ICLC, human and murine interferons (hIFN/mIFN), the 2-cyanaziridin BM41.332 and lipopolysaccharide (LPS). By using IFN neutralizing antibodies it was further shown, that the induction of GM-CSF release by monocytes/macrophages is independent of IFN secretion by these cells. The above BRMs, except hIFN, simultaneously stimulated the release of prostaglandin (PgE), which contributes to a negative feedback mechanism for GM-CFU-C growth. In vivo treatment with these BRMs resulted also in an increase in serum GM-CSF titers, as well as increased release of GM-CSF and PgE by macrophages and bone marrow cells. The in vitro/in vivo release of the inhibitory factor PgE could be selectively inhibited by Indomethacin, leaving the release of GM-CSF intact. The present results support the concept that some BRMs might be of value in reconstituting or protecting granulocyte and monocyte/macrophage function.